Fabrication of a Monolithic Implantable Neural Interface from Cubic Silicon Carbide.

One of the main issues with micron-sized intracortical neural interfaces (INIs) is their long-term reliability, with one major factor stemming from the material failure caused by the heterogeneous integration of multiple materials used to realize the implant. Single crystalline cubic silicon carbide (3C-SiC) is a semiconductor material that has been long recognized for its mechanical robustness and chemical inertness. It has the benefit of demonstrated biocompatibility, which makes it a promising candidate for chronically-stable, implantable INIs. Here, we report on the fabrication and initial electrochemical characterization of a nearly monolithic, Michigan-style 3C-SiC microelectrode array (MEA) probe. The probe consists of a single 5 mm-long shank with 16 electrode sites. An ~8 µm-thick p-type 3C-SiC epilayer was grown on a silicon-on-insulator (SOI) wafer, which was followed by a ~2 µm-thick epilayer of heavily n-type (n+) 3C-SiC in order to form conductive traces and the electrode sites. Diodes formed between the p and n+ layers provided substrate isolation between the channels. A thin layer of amorphous silicon carbide (a-SiC) was deposited via plasma-enhanced chemical vapor deposition (PECVD) to insulate the surface of the probe from the external environment. Forming the probes on a SOI wafer supported the ease of probe removal from the handle wafer by simple immersion in HF, thus aiding in the manufacturability of the probes. Free-standing probes and planar single-ended test microelectrodes were fabricated from the same 3C-SiC epiwafers. Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were performed on test microelectrodes with an area of 491 µm2 in phosphate buffered saline (PBS) solution. The measurements showed an impedance magnitude of 165 kΩ ± 14.7 kΩ (mean ± standard deviation) at 1 kHz, anodic charge storage capacity (CSC) of 15.4 ± 1.46 mC/cm2, and a cathodic CSC of 15.2 ± 1.03 mC/cm2. Current-voltage tests were conducted to characterize the p-n diode, n-p-n junction isolation, and leakage currents. The turn-on voltage was determined to be on the order of ~1.4 V and the leakage current was less than 8 µArms. This all-SiC neural probe realizes nearly monolithic integration of device components to provide a likely neurocompatible INI that should mitigate long-term reliability issues associated with chronic implantation.

Microchannel-based regenerative scaffold for chronic peripheral nerve interfacing in amputees.

Neurally controlled prosthetics that cosmetically and functionally mimic amputated limbs remain a clinical need because state of the art neural prosthetics only provide a fraction of a natural limb's functionality. Here, we report on the fabrication and capability of polydimethylsiloxane (PDMS) and epoxy-based SU-8 photoresist microchannel scaffolds to serve as viable constructs for peripheral nerve interfacing through in vitro and in vivo studies in a sciatic nerve amputee model where the nerve lacks distal reinnervation targets. These studies showed microchannels with 100 µm × 100 µm cross-sectional areas support and direct the regeneration/migration of axons, Schwann cells, and fibroblasts through the microchannels with space available for future maturation of the axons. Investigation of the nerve in the distal segment, past the scaffold, showed a high degree of organization, adoption of the microchannel architecture forming 'microchannel fascicles', reformation of endoneurial tubes and axon myelination, and a lack of aberrant and unorganized growth that might be characteristic of neuroma formation. Separate chronic terminal in vivo electrophysiology studies utilizing the microchannel scaffolds with permanently integrated microwire electrodes were conducted to evaluate interfacing capabilities. In all devices a variety of spontaneous, sensory evoked and electrically evoked single and multi-unit action potentials were recorded after five months of implantation. Together, these findings suggest that microchannel scaffolds are well suited for chronic implantation and peripheral nerve interfacing to promote organized nerve regeneration that lends itself well to stable interfaces. Thus this study establishes the basis for the advanced fabrication of large-electrode count, wireless microchannel devices that are an important step towards highly functional, bi-directional peripheral nerve interfaces.

Regenerative scaffold electrodes for peripheral nerve interfacing.

Advances in neural interfacing technology are required to enable natural, thought-driven control of a prosthetic limb. Here, we describe a regenerative electrode design in which a polymer-based thin-film electrode array is integrated within a thin-film sheet of aligned nanofibers, such that axons regenerating from a transected peripheral nerve are topographically guided across the electrode recording sites. Cultures of dorsal root ganglia were used to explore design parameters leading to cellular migration and neurite extension across the nanofiber/electrode array boundary. Regenerative scaffold electrodes (RSEs) were subsequently fabricated and implanted across rat tibial nerve gaps to evaluate device recording capabilities and influence on nerve regeneration. In 20 of these animals, regeneration was compared between a conventional nerve gap model and an amputation model. Characteristic shaping of regenerated nerve morphology around the embedded electrode array was observed in both groups, and regenerated axon profile counts were similar at the eight week end point. Implanted RSEs recorded evoked neural activity in all of these cases, and also in separate implantations lasting up to five months. These results demonstrate that nanofiber-based topographic cues within a regenerative electrode can influence nerve regeneration, to the potential benefit of a peripheral nerve interface suitable for limb amputees.